Maximum Value, Limited Data, and Development to Inflection Points

Research and development costs to market authorization are formidable. Given the pattern of product attrition occurring throughout the development lifecycle, outsourcing decisions accentuate the importance of earlier phase clinical research from the time of IND enabling studies for first in human studies, through demonstration of target engagement and dose ranging.

Across phases, clinical protocols increasingly address multiple hypotheses. The structure and level of assessments are increasingly complex whether based upon number or type of procedures, work burden, or cost. As many products achieving approval are derived from smaller pharmaceutical and biopharmaceutical organizations with constrained staffing, an ability to amplify the effectiveness of development teams by strategic outsourcing is mandatory. This is particularly important for clinical trial services given a tendency to repetitively engage the same centers with exceptional research capabilities and the need for informed site engagement. Given product sophistication, and the refined patient phenotypes now targeted, a disciplined therapeutic focus has best prospects for success.

Doing More with Less

The decade that normally occurs from product conceptualization to marketing approval leaves proprietary patent life to approximately 10 years. This R&D landscape results in more complex and aggressively implemented programs, with a greater emphasis upon technology for acquisition of research data, as well as tracking to project milestones. In aggregate, accelerated programs protect intellectual property, access government incentives facilitating development, and exploit regulatory flexibility in standards for product approval. Minimizing patient sample– particularly for rare diseases–while maximizing experimental treatment for all patients is dominant.

"The decade that normally occurs from product conceptualization to market exclusivity leaves proprietary patent life to approximately 10 years"

Innovation in trial design occurs in tandem with enhanced execution which exploits technological innovation for data acquisition and decision-making. A mandate exists to quickly move through the development cycle informing a complex set of outcomes demanded by multiple stakeholders. An “inflection point” research and development strategy therefore develops in which key business decisions require predictable study metrics, and real-time data tracking. Given this dynamic, product “value” in early phase research is defined across variables including safety, predictable exposure, target engagement and proof of concept studies using populations optimized for signal detection. Additionally, although pursuing well-established and predictable development pathways has merit, innovative strategies exploit “nearest neighbor” indications by creating programs simultaneously evaluating molecular targets common to many indications (e.g., a basket strategy).

Assuring patient access following approval becomes a strategic R&D objective and programs that resonate with diverse stakeholders are common. In contrast to the homogeneous and highly leveraged populations of common early phase trials, a mix of patients with concomitant medications and co morbidities driving increased healthcare utilization is ideal, preferably if data are obtained in representative treatment settings. Studies sampling outcomes (rather than measures) while assessing the interaction of novel with established therapy better inform the value of new treatments. Registries created at the onset of registration programs examine disease trajectory, disease burden, inform future study designs, and on occasion support registration. Wearable devices and web-based platforms for data acquisition enable evidence generation.

The challenges of “breakthrough”

Accelerated approval pathways facilitate product registration for disorders with unmet clinical needs but frequently result in less overall clinical data than traditionally encountered at the time of product approval. The limitation of these “breakthrough” designations particularly encumbers decision-makers dictating product access and requires pre-and post-registration activities to inform value. Techniques that are useful extract healthcare utilization by “piggybacking” upon randomized controlled trials, examine healthcare utilization within open label extensions, create retrospective chart reviews or claims-based analyses in “before–after” designs, or exploit other forms of observational research such as prospective cohort studies for screen failure patients providing a proxy for those included in randomization.

Virtual Relationships

Sponsor/CRO relationships historically were transactional and characterized by single entry points for functional services. Frequently outsourcing occurred only when there was limited internal capacity and tactical relationships placed a premium upon cost. This strategy now occurs on a continuum from preferred provider relationships, through partnering, alliances, and full integration. Complex, compressed research and development strategies which emphasize decision-making in earlier phase clinical research particularly are suited to an integrated organizational approach.

Research and development teams have been characterized as matrix organizations in which individuals with content expertise develop a common mission for product development. Virtual teams, which are geographically dispersed, separated through time, and communicate electronically, now are customary when outsourcing services are dominant. Although teams make more effective product development decisions than individuals, virtual teams with enhanced electronic capabilities counter intuitively may be the most effective. As current R&D relationships expand the use of virtual organizations, transformational leadership and enabling technology that links functional activities with inspirational vision will be associated with project success.